The primary cilium is a solitary, non-motile microtubule-based organelle that protrudes outwards from the surface of most normal eukaryotic cells. Upon in-depth investigation, it has been found to participate actively in various intercellular signaling pathways in mammals, e.g. Hedgehog (Hh), Wingless (Wnt) and PDGFRa, for cell migration, homeostasis, and cell cycle regulation. It also functions as the multisensory antenna of the cells towards external stimuli, such as chemical, temperature, and pressure stimuli.
Recently, a renaissance on the research of its structure was initiated by substantial new and overwhelming evidence in support of its significant correlation with many human diseases and developmental disorders (collectively known as ciliopathies). For instance, dysfunctions of primary cilium signaling have been found to correlate strongly in human polycystic kidney diseases, epithelial ovarian cancer, as well as aberrant skeletal development; the absence of primary cilia and overexpression of proteins nearby have also well been observed throughout the stages of pancreatic, breast, and prostate tumorigenesis.
That said, very little have the roles of primary cilium been clearly and fully known so far, with the lack of direct and specific imaging methods, for example visible-to-near-infrared fluorescence imaging and magnetic resonance imaging, being a critical factor. There are so many organelle-specific markers currently available for mitochondria, Golgi apparatus, and lysosome; however, visualization of primary cilia, to date, can only be achieved through immunostaining using antibodies or green fluorescent proteins, as no primary cilium-specific probes have been reported in literature. Such two indirect means are always challenged with fixation and delivery issues, while auto-fluorescence is inevitable and the amount of information obtained through them is limited.
To address all the above problems, using a direct and specific imaging tool incorporated with lanthanide ions is a promising solution. The long emission lifetimes (micro to millisecond region), hypersensitive, sharp and fingerprint spectral profile of europium, paired with a time-gated system, can effectively eliminate the interfering autofluorescence as well as allowing the specific imaging of primary cilium in a time-resolved manner in vitro or in vivo.
Therefore, it turns out to be a need for simplicity of the design and synthesis of a complex which exhibits the specific subcellular localization in the primary cilium.
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